Review
Biochemistry & Molecular Biology
Soji Morishita, Norio Komatsu
Summary: BCR::ABL1-negative myeloproliferative neoplasms (MPNs) are hematopoietic malignancies caused by acquired somatic mutations in hematopoietic stem/progenitor cells, leading to abnormal blood cell proliferation and bone marrow fibrosis. Common mutations in BCR::ABL1-negative MPNs include JAK2, MPL, and CALR, which are crucial for diagnosing these diseases. Moreover, comprehensive genetic and expression analyses have identified additional gene mutations, such as ASXL1, EZH2, IDH1/2, SRSF2, and U2AF1, associated with the prognosis of BCR::ABL1-negative MPNs. Single-cell analyses have provided insights into the order of mutation acquisition and the pathogenesis of these MPNs. Additionally, specific CREB3L1 overexpression in megakaryocytes and platelets may hold promise for diagnostic applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Genetics & Heredity
Aleksandra Mroczkowska-Bekarciak, Tomasz Wrobel
Summary: BCR::ABL1-negative myeloproliferative neoplasms are clonal diseases with characteristic driver mutations in genes including JAK2, CALR, or MPL. The diagnosis of these neoplasms relies on the detection of mutations in these genes. New technologies like next-generation sequencing have opened up new possibilities for finding additional mutations, which can aid in risk stratification, disease progression assessment, transformation to AML, and treatment selection.
FRONTIERS IN GENETICS
(2023)
Review
Cell Biology
Norman Abbou, Pauline Piazzola, Jean Gabert, Vincent Ernest, Robin Arcani, Anne-Laure Couderc, Antoine Tichadou, Pauline Roche, Laure Farnault, Julien Colle, L'houcine Ouafik, Pierre Morange, Regis Costello, Geoffroy Venton
Summary: BCR-ABL1-negative myeloproliferative neoplasms (MPNs) include three major subgroups - polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). They are characterized by abnormal hematopoietic proliferation and an increased risk of leukemic transformation. In addition to the driver mutations JAK2, CALR, and MPL, more than twenty additional mutations have been identified through next-generation sequencing (NGS), which may be involved in pathways related to epigenetic modifications, RNA splicing, or DNA repair. This review highlights the impact of molecular biology on the diagnosis, prognosis, and therapeutic management of PV, ET, and PMF patients.
Review
Biochemistry & Molecular Biology
Dominik Kiem, Sandro Wagner, Teresa Magnes, Alexander Egle, Richard Greil, Thomas Melchardt
Summary: Philadelphia chromosome negative myeloproliferative neoplasms consist of polycythemia vera, essential thrombocytosis, and primary myelofibrosis. Mutations in JAK2, MPL, or CALR characterize these disorders, with additional mutations leading to myeloid cell lineages expansion and marrow fibrosis in PMF. Chronic inflammation plays a significant role in the disease initiation and progression, with neutrophilic granulocytes playing a major role in the pathogenesis of thromboembolic events.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Graeme Greenfield, Mary Frances McMullin, Ken Mills
Summary: Philadelphia negative myeloproliferative neoplasms (MPN) constitute a heterogeneous group of clonal myeloid stem cell disorders, including polycythaemia vera, essential thrombocythaemia and primary myelofibrosis. These disorders are characterized by constitutive activation of the JAK/STAT signaling pathway, often with driving mutations in JAK2, CALR and MPL. Co-occurring epigenetic factors may also play a role, while prognostic implications vary depending on disease phenotype, genotype and other external factors.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Medical Laboratory Technology
Namhee Kim, Hyunwoong Park, Sue Shin, Jong-Hyun Yoon, Eun-Youn Roh
Summary: This study aimed to investigate changes in the diagnosis and subtype classification of Korean patients with BCR-ABL1-negative MPN related to the revision of the WHO classification in 2016. The results found that with the application of the 2016 classification, some cases of ET were reclassified as pre-PMF, and the proportion of PV increased. These findings have important implications for accurately defining disease subtypes and providing personalized treatment for patients.
CLINICAL LABORATORY
(2022)
Review
Biochemistry & Molecular Biology
Erika Morsia, Elena Torre, Antonella Poloni, Attilio Olivieri, Serena Rupoli
Summary: Despite their differences in clinical presentation, myeloproliferative neoplasms (MPN) share similarities in morphology, propensity for thrombotic events and leukemia transformation, and a complex molecular pathogenesis. Key driver mutations, such as JAK2, MPL, and CALR, activate the JAK-STAT signaling pathway, which is characteristic of MPN pathogenesis. Recent research has revealed the presence of co-occurring somatic mutations associated with epigenetic regulation, mRNA splicing, transcriptional mechanisms, signal transduction, and DNA repair mechanisms in MPN patients. Integrating genetic information into clinical practice has already improved disease monitoring and provided prognostic information regarding disease progression. While current therapeutic approaches have limited disease-modifying activity, a deeper understanding of the genetic basis of MPN has identified potential targets for targeted therapies. This review aims to explore the molecular landscape of MPN, providing a comprehensive overview of driver mutations, additional mutations, their impact on pathogenesis, prognostic value, and future implications for therapeutic management.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medical Laboratory Technology
Namhee Kim, Hyunwoong Park, Sue Shin, Jong-Hyun Yoon, Eun-Youn Roh
Summary: The diagnosis and subtype classification of BCR-ABL1-negative MPN patients in Korea have changed with the revision of the WHO classification in 2016. The proportion of PV increased and there were significant differences in CBC between different subtypes of MPN.
CLINICAL LABORATORY
(2022)
Article
Oncology
Salem Alshemmari, Mazyad Almazyad, Aisha Alwehaib, Reem Ameen
Summary: The study investigated the epidemiology of Ph-negative MPNs among Kuwaiti nationals, revealing ET as the most common subtype and JAK2V617F as the most common driver mutation. A significant percentage of patients (19.2%) presented with thrombosis at diagnosis, with males more likely to have arterial thrombosis and females more likely to have venous thrombosis.
Review
Hematology
Ivan Krecak, Srdan Verstovsek, Marko Lucijanic
Summary: The exact prognostic role of cardiovascular risk factors in BCR-ABL1 negative MPN patients is unknown. Current treatment of CV risk factors in MPNs is not guided by the presence of these risk factors. Target levels for different metabolic deflections in MPNs have not been defined. This review discusses the important aspects of individual CV risk factors in MPNs, summarizes recent advances, and proposes future directions and research areas.
ANNALS OF HEMATOLOGY
(2023)
Article
Oncology
Li Ding, Jie Luo, Jing Zhang, Ji Wang, Zhao Li, Juan Huang, Li Chai, Jiao Mu, Beibei Zhao, Yi Zhong, Lin Zhang, Lin Liu
Summary: SPAG6, a newly identified cancer-testis antigen, has been shown to contribute to the occurrence and development of BCR/ABL1-negative MPNs. Its expression levels have been found to be associated with disease phenotype and can serve as a potential biomarker for distinguishing MPN cases from healthy individuals.
Article
Hematology
Nur Atikah Zakaria, Norfifiana Alisa Rosle, Mat Jusoh Siti Asmaa, Sudin Aziee, Mohd Yassim Haiyuni, Nurul Ameera Samat, Azlan Husin, Rosline Hassan, Marini Ramli, Shafini Mohamed Yusoff, Ibrahim Khidir Ibrahim, Hamid Ali Nagi Al-Jamal, Muhammad Farid Johan
Summary: CALR mutations are key markers in the molecular diagnosis of myeloproliferative neoplasms, especially in patients without JAK2 V617F mutation. This study demonstrated that CSGE is an inexpensive, sensitive, and reliable alternative method for detecting CALR mutations in BCR-ABL1-negative MPN patients, identifying various mutation types not detected by AS-PCR.
INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Valeria Di Battista, Maria Teresa Bochicchio, Giulio Giordano, Mariasanta Napolitano, Alessandro Lucchesi
Summary: The past decade has seen significant advancements in the understanding of chronic myeloproliferative neoplasms through preclinical research. The translational implications of these new biological discoveries inform future therapeutic strategies, with a focus on the role of inflammasomes in guiding and impacting the disease's natural history. Greater knowledge in this area has the potential to lead to improved care for patients with MPNs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Medicine, General & Internal
Giovanni Fulvio, Chiara Baldini, Marta Mosca, Antonello di Paolo, Guido Bocci, Giuseppe Alberto Palumbo, Emma Cacciola, Paola Migliorini, Rossella Cacciola, Sara Galimberti
Summary: This article reviews possible mechanisms linking clonal hematopoiesis of indeterminate potential (CHIP) to chronic myeloproliferative neoplasms (MPNs), autoimmune diseases (ADs), and cardiovascular diseases (CADs). The presence of CHIP may be associated with immune reactions and thrombosis.
FRONTIERS IN MEDICINE
(2023)
Review
Oncology
Panagiotis T. Diamantopoulos, Nora-Athina Viniou
Summary: Atypical chronic myelogenous leukemia (aCML) is a rare myelodysplastic/myeloproliferative neoplasm. Recent advances in molecular characterization have improved understanding, accurate classification and diagnosis of the disease, identified adverse prognostic factors, and expanded therapeutic choices for patients.
FRONTIERS IN ONCOLOGY
(2021)
Article
Nutrition & Dietetics
Claudia Martinez-Tapia, Thomas Diot, Nadia Oubaya, Elena Paillaud, Johanne Poisson, Mathilde Gisselbrecht, Laure Morisset, Philippe Caillet, Aurelie Baudin, Frederic Pamoukdjian, Amaury Broussier, Sylvie Bastuji-Garin, Marie Laurent, Florence Canoui-Poitrine
Summary: The study found that only older obese women with cancer who had minimal weight loss before diagnosis had a lower risk of mortality compared to normal-weight counterparts. However, overweight and obese men did not have a lower mortality risk regardless of weight loss.
AMERICAN JOURNAL OF CLINICAL NUTRITION
(2021)
Article
Immunology
Emmanuel Weiss, Pierre de la Grange, Mylene Defaye, Juan Jose Lozano, Ferran Aguilar, Pushpa Hegde, Ariane Jolly, Lucile Moga, Sukriti Sukriti, Banwari Agarwal, Haqeeqat Gurm, Marion Tanguy, Johanne Poisson, Joan Claria, Paer-Selim Abback, Axel Perianin, Gautam Mehta, Rajiv Jalan, Claire Francoz, Pierre-Emmanuel Rautou, Sophie Lotersztajn, Vicente Arroyo, Francois Durand, Richard Moreau
Summary: Patients with ACLF exhibit dysregulation of blood immune cells, including increased neutrophils and M0-like monocytes, as well as depletion of various lymphocyte subsets. These immune cell alterations, along with defective neutrophil superoxide anion production, may contribute to immunosuppression in ACLF, highlighting potential targets for future therapies.
FRONTIERS IN IMMUNOLOGY
(2021)
Editorial Material
Medicine, Research & Experimental
Johanne Poisson, Marion Tanguy, Pierre-Emmanuel Rautou
M S-MEDECINE SCIENCES
(2021)
Article
Geriatrics & Gerontology
Johanne Poisson, Claudia Martinez-Tapia, Damien Heitz, Romain Geiss, Gilles Albrand, Claire Falandry, Mathilde Gisselbrecht, Anne-Laure Couderc, Rabia Boulahssass, Evelyne Liuu, Pascaline Boudou-Rouquette, Anne Chah Wakilian, Cedric Gaxatte, Frederic Pamoukdjian, Laure de Decker, Valery Antoine, Catherine Cattenoz, Heidi Solem-Laviec, Olivier Guillem, Hayat Medjenah, Pierre Andre Natella, Florence Canoui-Poitrine, Marie Laurent, Elena Paillaud
Summary: More than half of older cancer patients in geriatric oncology clinics have cachexia, associated with factors including cancer site, metastases, performance status, mobility, surgical history, cognitive disorders, risk of depression, and poor food intake. Cachexia independently predicts 6-month mortality.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2021)
Article
Nutrition & Dietetics
Elena Paillaud, Johanne Poisson, Clemence Granier, Antonin Ginguay, Anne Plonquet, Catherine Conti, Amaury Broussier, Agathe Raynaud-Simon, Sylvie Bastuji-Garin
Summary: This study investigated the association between serum leptin levels and healthcare-associated infections in hospitalized older patients. The results showed that women with lower leptin levels were more likely to experience healthcare-associated infections, and this association may be mediated by nutritional status.
Article
Oncology
Fiamma Burgassi, Elena Paillaud, Johanne Poisson, Guilhem Bousquet, Frederic Pamoukdjian
Summary: The study assessed the prognostic value of CAR trajectories among older adults with cancer and identified two clusters with significantly different overall survivals. Patients with higher CAR values were associated with frailty, metastatic disease, high CRP levels, and low albumin levels, suggesting a cancer-cachexia trajectory.
Article
Hematology
Pierre Laporte, Marie Tuffigo, Anne Ryman, Mathieu Fiore, Etienne Riviere, Chloe James, Alexandre Guy
Summary: The study aimed to evaluate the performance of VWF:GPIbR with HemosIL VWF:RCo Werfen versus VWF:RCo in patients with thrombocytosis in the context of MPNs and in patients with secondary thrombocytosis.
THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Oncology
Catherine Conti, Frederic Pamoukdjian, Thomas Aparicio, Soraya Mebarki, Johanne Poisson, Gilles Manceau, Julien Taieb, Bastien Rance, Sandrine Katsahian, Anais Charles-Nelson, Elena Paillaud
Summary: This study aims to investigate the prognostic factors and chemotherapy efficacy in older patients (≥70 years) with metastatic pancreatic cancer (mPC). The results showed that gemcitabine + nab-paclitaxel regimen and anti-diabetic therapy were associated with better overall survival, while impaired functional status, liver metastases, and high neutrophil count were associated with worse overall survival.
Article
Multidisciplinary Sciences
Rida Al-Rifai, Marie Vandestienne, Jean-Remi Lavillegrand, Tristan Mirault, Julie Cornebise, Johanne Poisson, Ludivine Laurans, Bruno Esposito, Chloe James, Olivier Mansier, Pierre Hirsch, Fabrizia Favale, Rayan Braik, Camille Knosp, Jose Vilar, Giuseppe Rizzo, Alma Zernecke, Antoine-Emmanuel Saliba, Alain Tedgui, Maxime Lacroix, Lionel Arrive, Ziad Mallat, Soraya Taleb, Marc Diedisheim, Clement Cochain, Pierre-Emmanuel Rautou, Hafid Ait-Oufella
Summary: JAK2V617F mutation drives vascular resident macrophages toward a pathogenic phenotype and promotes dissecting aortic aneurysm.
NATURE COMMUNICATIONS
(2022)
Article
Hematology
Noemie Gensous, Wendy Jourde, Kevin Salles, Chloe James, Alexandre Guy, Pierre Duffau
Summary: Bilateral adrenal hemorrhage is a rare cause of adrenal insufficiency, and its association with myeloproliferative neoplasms is uncommon. This case report describes two octogenarian males with JAK2 V617F-positive essential thrombocythemia presenting with abdominal pain, malaise, and fatigue. Both patients were on long-term direct oral anticoagulant treatment for atrial fibrillation. Favorable outcomes were achieved with steroid replacement therapy, cytoreduction, aspirin, and switching to vitamin K antagonists.
BLOOD COAGULATION & FIBRINOLYSIS
(2023)
Article
Hematology
Alexandre Guy, Khalil Helzy, Olivier Mansier, Jean-Claude Bordet, Etienne Riviere, Mathieu Fiore, Chloe James
Summary: This study aimed to explore and compare platelet function in patients with different MPN molecular markers. The results showed no significant defects in platelet function in patients with CALR mutations compared to the healthy control group. Therefore, these findings do not support the hypothesis that calreticulin-mutated platelets have platelet function defects that could explain the lower thrombotic risk in CALR patients.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Etienne Riviere, Rodolphe Thiebaut, Estibaliz Lazaro, Alexandre Guy, Chloe James, Olivier Mansier, Patrick Blanco, Jean-Francois Viallard
Summary: Immune thrombocytopenia (ITP) is a condition characterized by a low platelet count that can lead to life-threatening hemorrhages. Rituximab, an anti-CD20 antibody, has shown promising results in treating persistent/chronic ITP. A study retrospectively analyzed the clinical courses and blood lymphocyte subset data of 72 patients treated with rituximab. It was found that a low number of circulating NK cells was associated with a complete response to rituximab.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Nutrition & Dietetics
Claudia Martinez-Tapia, Kevin Rougette, Virginie Fossey-Diaz, Tristan Cudennec, Cherifa Taleb, Laurent Balardy, Cecile Mertens, Nathalie Mitha, Michael Bringuier, Karin Maley, Sandrine Estivin, Valerie Quipourt, Florence Canoui-Poitrine, Capucine Baldini, Johanne Poisson, Elena Paillaud
Summary: Older cancer patients have an increased risk of sarcopenia, which can be determined through criteria such as abnormal strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F), low hand-grip strength (HGS), low arm circumference (AC), and low physical performance (PP). The prevalence of sarcopenia and severe sarcopenia in this study population was 24.5% and 11.7%, respectively. Sarcopenia was found to be strongly predictive of 6-month mortality in patients with metastatic cancer.
Meeting Abstract
Gastroenterology & Hepatology
Victoire De Salins, Antoine Morel, Claudia Martinez-Tapia, Pierre-Emmanuel Rautou, Florence Canoui-Poitrine, Elena Paillaud, Johanne Poisson
JOURNAL OF HEPATOLOGY
(2022)
